title: Tumor necrosis factor-alpha mRNA-positive cells in spontaneous resorption in rodents.
abstract: OBJECTIVE
  It has been proposed that high rates of resorption/spontaneous abortion may result from interaction in the decidua of gamma-interferon-producing natural killer (NK) cells and tumor necrosis factor (TNF)-alpha-producing macrophages. An increased release of TNF-alpha from placental tissue of resorptions has been reported, but macrophages producing TNF-alpha have so far not been demonstrated at the feto-maternal interface. Therefore, we have sought to identify TNF-alpha-producing cells by in situ hybridization at the feto-maternal interface in two inbred, well-characterized, and stable strains of laboratory rodents with high and low resorption rates.
  
  
  METHODS
  Pregnant DBA/2-mated CBA/J mice with a resorption rate of 20% to 30% (dependent on NK cells and macrophages) and diabetes-resistant Bio-Breeding/Edinburgh (DR-BB/E) rats with low resorption rates (presumed to result from chromosomal abnormalities) were studied. AsialoGM1+ cells were detected by immunohistochemistry, and TNF-alpha mRNA+ cells were detected by in situ hybridization.
  
  
  RESULTS
  TNF-alpha mRNA+ cells were detected in DBA/2-mated CBA/J mice at the time of resorption but only at the trophoblast-decidual junction. AsialoGM1+ cells were present in decidua, as assessed by immunohistochemistry, but few if any gave a positive signal for TNF-alpha. In rat resorptions, TNF-alpha mRNA-positive cells were present within the yolk sac and in contact with the trophoblast, but not at the trophoblast-decidual junction. In neither species did a significant accumulation of detectable TNF-alpha mRNA+ cells occur before the usual time of onset of resorption.
  
  
  CONCLUSIONS
  In the DBA/2-mated CBA/J mouse, the removal of the placenta is associated with removal of a thin rim of adherent decidua similar to the location of the TNF-alpha mRNA+ cells detected in this study. Our data suggest that increased TNF-alpha in tissues associated with failing feto-placental units may arise from infiltration/activation of scavenger cells from decidua that are likely to be macrophages. Local TNF-alpha production in decidua, which occurs as a prelude to resorption in the CBA x DBA/2 model, could not be detected due to the insensitivity of the TNF-alpha probe we used; the release of TNF-alpha from decidual tissue left after the removal of the placenta does not differ between resorbing and healthy implant sites. AsialoGM1+ cells did not seem to be major producers of TNF-alpha. TNF-alpha mRNA+ cells in a low rate of resorption (rat) model were only found on the fetal side of the trophoblast, and they may also represent a macrophage response (to dying embryo tissue) derived from a nondecidual source. The location of TNF-alpha mRNA+ cells may identify distinct and different mechanisms of resorption in rodents.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Edinburgh, Scotland.
authors.forename: R G
authors.initials: RG
authors.lastname: Lea
authors.forename: S
authors.initials: S
authors.lastname: McIntyre
authors.forename: J D
authors.initials: JD
authors.lastname: Baird
authors.forename: D A
authors.initials: DA
authors.lastname: Clark
mesh_terms: D000034:Abortion, Veterinary / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D003656:Decidua / Q000166:cytology* / Q000378:metabolism*; D020964:Embryo Loss / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D017403:In Situ Hybridization; D007694:Killer Cells, Natural / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha